Size and Shell Effects on the Photoacoustic and Luminescence Properties of Dual Modal Rare-Earth-Doped Nanoparticles for Infrared Photoacoustic Imaging

Infrared-emitting rare-earth (ytterbium and erbium) doped nanoparticles (REDNPs) have recently emerged as an excellent probe for both deep tissue luminescence and photoacoustic (PA) imaging with high resolutions and contrast. Here we report on the first study of the size and surface effects of the infrared PA imaging of dual modal REDNPs. We show that the PA signal amplitude generated by REDNPs is increased by increasing the size and coating the inorganic shell (undoped NaYF₄ or silica). We have also discovered that the choice of the coating material is critical as undoped NaYF₄ shell was able to enhance PA signal amplitude (by up to ∼30%) and infrared emission (19 times) simultaneously. The simultaneous enhancement of PA signal amplitude and infrared emission was due to increased phonon modes and reduced surface effects. The in vivo PA images obtained demonstrated that in addition to being excellent luminescent probes, the REDNPs also performed as successful PA contrast agents to visualize rodent cortical blood vessels

Activation of sphingosine 1-phosphate receptor 2 attenuates chemotherapy-induced neuropathy

Platinum-based therapeutics are used to manage many forms of cancer, but frequently result in peripheral neuropathy. Currently, the only option available to attenuate chemotherapy-induced neuropathy is to limit or discontinue this treatment. Sphingosine 1-phosphate (S1P) is a lipid-based signaling molecule involved in neuroinflammatory processes by interacting with its five cognate receptors: S1P1–5. In this study, using a combination of drug pharmacodynamic analysis in human study participants, disease modeling in rodents, and cell-based assays, we examined whether S1P signaling may represent a potential target in the treatment of chemotherapy-induced neuropathy

Minimal clinically important difference of the EORTC QLQ-CIPN20 for worsening peripheral neuropathy in patients receiving neurotoxic chemotherapy

Context/objectives This is the first study to determine the minimal clinically important difference (MCID) of the European Organisation of Research and Treatment of Cancer Quality of Life Questionnaire-CIPN twenty-item scale (EORTC QLQCIPN20), a validated instrument designed to elicit cancer patients’ experience of symptoms and functional limitations related to chemotherapy-induced peripheral neuropathy. Methods Cancer patients receiving neurotoxic chemotherapy completed EORTC QLQ-CIPN20 and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity [FACT/GOG-NTX] at baseline, second cycle of chemotherapy (T2, n = 287), and 12 months after chemotherapy (T3, n = 191). Anchor-based approach used the validated FACT/GOG-NTX neurotoxicity (Ntx) subscale to identify optimal MCID cutoff for deterioration. Distribution-based approach used one-third standard deviation (SD), half SD, and one standard error of measurement of the total EORTC QLQ-CIPN20 score. Results There was a moderate correlation between the change scores of the Ntx subscale and sensory and motor subscales of QLQ-CIPN20 (T2: r = − 0.722, p < 0.001 and r = − 0.518, p < 0.001, respectively; T3: r = − 0.699; p < 0.001 and r = − 0.523, p < 0.001, respectively). The correlation between the change scores of the Ntx subscale and the QLQ-CIPN20 autonomic subscale was poor (T2: r = − 0.354, p < 0.001; T3: r = 0.286, p < 0.001). Based on the MCID derived using distribution-based method, the MCID for the QLQ-CIPN20 sensory subscale was 2.5–5.9 (6.9% to 16.4% of the subdomain score) and for motor subscale was 2.6–5.0 (8.1%–15.6% of the subdomain score). Conclusion The MCID for the EORTC QLQ-CIPN20 established using distribution-based approaches was 2.5–5.9 for the sensory subscale and 2.6–5.0 for the motor subscale. When noted in assessments even with small change in scores, clinicians can be alerted for appropriate intervention

NDRG1 Analyses.

<p>2A. Correlation of NDRG1 scores between investigator 1 and investigator. 2B. Mean NDRG1 expression scores in nerve tissue in subjects who did or did not develop paclitaxel-induced severe neuropathy. 2C. ROC analysis of predictive validity of NDRG1 for paclitaxel-induced severe neuropathy.</p

NDRG1 expression in normal nerve tissue.

<p>Photo micrographs (x 40 objective) depicting NDRG1 IHC, scale bar is 50μm. A: Score 0: Nerve highlighted by circles, with no expression of NDRG1. B: Score 1: Minimal expression of NDRG1 in less than 50% of the nerve bundle. C: Score 2: Strong expression of NDRG1 in less than 50% of the nerve bundle. D: Score 3: Strong expression of NDRG1 in more than 50% of the nerve bundle</p

Patient Characteristics.

<p>Patient Characteristics.</p